Fragile X syndrome is the most common inherited cause of mental retardation, and unintelligible speech is a very common characteristics of young males with fragile X syndrome (FXS). It is unclear what aspects of speech (e.g., rate, prosody, oral structure/function, articulation, phonological processes) cause poor intelligibility. Furthermore, it has not been determined what is the role of motor speech/FMR1 protein (FMRP) levels, cognitive/linguistic factors, and the communicative context in affecting intelligibility of conversational speech of males with FXS. Identifying these factors is important because the ability to be understood is critical for effective communication, and poor speech intelligibility compromises all aspects of daily verbal interactions. The proposed study builds on a currently funded R0-3 pilot study Hearing and Speech of Young with Males with Fragile X Syndrome, funded by the RFA "Neurobiology and Genetics of Fragile X Syndrome" in April of 2001, which examined at one point in time the speech and hearing skills of young males with fragile X syndrome. The proposed research will expand this research by examining longitudinally over a five year period the factors that affect changes in the speech intelligibility of 8 to 12 year old males with FXS in comparison to developmental age matched males with Down syndrome (DS) and males who are typically developing (TD). It will identify if motor speech/FMRP levels, cognitive/linguistic factors, and the social demands of the communicative context affect speech intelligibility. The specific objectives of this study are to: a) compare the development of phonological, prosodic, and segmental factors in the speech of males with FXS, males with DS, and TD males; b) identify the phonological, prosodic, and segmental factors affecting the speech intelligibility in conversational speech of males with FXS and determine if similar patterns of association are observed among males with DS and TD males; and c) to identify the motor speech/FMRP, cognitive/linguistic, and communicative contextual factors associated with speech intelligibility in conversational speech among males with FXS, and determine if similar patterns of association are observed among males with DS and TD males. Sixty males with FXS between 8 and 12 years of age, 40 males with Down syndrome between 8 and 12 years of age and 40 typically developing males matched for nonverbal intelligence age will be followed for five years. Speech production in isolated words, imitated sentences, spontaneous conversational speech, and narratives will be examined for prosodic and segmental features, phonological processes, and speech intelligibility for the three groups. In addition, children's oral motor skills, phonological processing, and selective listening will be examined. Fragile X DNA testing and FMRP analysis from blood samples will be done only on males with FXS. Growth curve methods will be used to quantify patterns of change over time in the overall level and rate of speech development including speech intelligibility. Of particular interest will be longitudinal analyses of speech intelligibility designed to determine the degree to which motor speech/FMRP, cognitive/linguistic, and contextual factors predict speech intelligibility among males with FXS. Subsequent analyses will ask whether factors associated with intelligibility among males with FXS are also associated among males with DS and TD males. Findings will contribute to a better understanding of the factors that affect speech intelligibility in young males with FXS and provide an essential knowledge base for speech intervention.